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Tuesday, October 10, 2006

One group of research gerontologists has set as its publicly
announced goal the demonstration of the reversal of aging in a
mouse by about 40% by 2012. See:

Strategies for Engineered Negligible Senescence (SENS I &
SENS II)

(http://research.mednet.ucla.edu/pmts/sens/sens1.htm)

(http://research.mednet.ucla.edu/pmts/sens/sens2.htm)

(http://research.mednet.ucla.edu/pmts/sens/sen2article.htm)

"Time to Talk SENS: Critqueing the Immutability of Human Aging"

"Is human aging still mysterious enough to be left only to
scientists?"

Caloric Restriction

It was demonstrated in 1935 that caloric restriction will slow
the rate of aging in rats by an amount roughly proportional to
the degree of caloric restriction. Several "longevinauts",
following the lead of Dr. Roy Walford, are trying this approach
to the retardation of aging. In the meantime, a study of caloric
restriction in primates is underway at two locations, and preliminary results suggest that
the same kinds of effects observed in other mammals are taking
place with the primates.

The Methuselah Gene

A Harvard spinoff is trying to bring to market a product or
products designed around the "Methuselah" gene that confers long
lives upon centenarians.

Will You Live Longer, and Prosper?

The bottom line is that you might want to keep in the back of
your head the possibility of a longer life than most of us have
planned. If this fails to materialize, it will be because of a
lack of faith in the possibility that this can happen.

I believe that the conquest of aging is feasible, and if it's
feasible, it will be accomplished somewhere by someone sometime.

How Can Babies Be Born Young?

Have you ever wondered how babies can be born young when the
cells that give rise to them may be from 15 to 70 years old? We
know of no way to totally rejuvenate either cells or people. Why
aren't babies born with an age that's some sort of average of the
ages of the cells that created it?

It's clear that every species must have some way of making
brand-spanking-new copies of its kind across countless
generations. Deviations (mutations) in the genetic specifications
defining the species may occur, but partial aging of new
organisms cannot be allowed to accumulate. Otherwise, life on
Earth (and we ourselves) wouldn't be here.

So what's happening?

Nature Must Know the Secret of Total Rejuvenation

It's clear that Nature has some means of completely rejuvenating
organisms at the time of the reproduction cycle, so that their
offspring have their biological clocks reset to zero.

The contents of the documents may change, but they will always be
printed on new paper. What's so striking about this is that,

It has to be perfect! If there were any cumulative aging
passed on to succeeding generations, they would eventually be
created too old to survive.

This has to be present for every life form on this planet
from their first instantiation onward. Otherwise, they wouldn't
be here. That means that we're looking for machinery that may be
found in the simplest, archeozoic prokaryote to the most modern,
complex eukaryote.

It has to be happening in unicellular life forms, as well as in
multicellular organisms that reproduce sexually or
parthenogenically. To say it again, Nature has been perfectly
rejuvenating organisms under our very noses since time
immemorial!

So how can we learn how to do this? One approach might be to
examine the simplest organisms.

I first became cognizant of this reality when I read Advanced
Cell Technology's announcement, in April, 2000, that they had
successfully cloned eight calves. What seemed striking to me in
that press release was the fact that the egg cells were
enucleated, and that somatic cells from a very old cow were
implanted in them in lieu of spermatozoa. Somehow, the
rejuvenation process took place in its customary way, and the
calves were born with longer telomeres than calves produced in
the conventional way. This raises a few questions:

Since the nuclei of the egg cells were no longer present, the
old and damaged nuclei of the somatic cells from the old cow must
somehow have been reconstituted so that they were young again.
More specifically, their telomeres were re-established. Another
crucial question might be: was genetic damage to these nuclei
completely reversed?

How did the somatic cells know that they were in egg cells?

Something in the cytoplasm of the egg cells must have
triggered the rejuvenation cycles, since the oöcyte's nuclei
was no longer present.

The rejuvenation cycles must have occurred rapidly, either in
the "fertilized zygotes" prior to mitosis, or in the daughter
cells immediately after mitosis.

This Reconstitution Process Must Occur in Protozoa As Well As In
Multicellular Organisms

This process must also take place in unicellular organisms that
reproduce by parthenogenesis. Either they have intrinsic
maintenance mechanisms that keep them always in the pink of
condition, or reconstitution must occur when they divide. In
other words, either cells that reproduce are immortal and
perfectly self-repairing, or perfect rejuvenation occurs when the
cell reproduces.

The first possibility, that germ plasm is
immortal, was advanced by Weisman in 1891. More recently, Leonard
Hayflick ("Mortality and Immortality at the Cellular Level",
Biochemistry (Moscow), Vol. 62 (1997), No.
111", has argued that unicellular organisms
are mortal, and that
rejuvenation only occurs when there is the periodic exchange or
reorganization of genetic material).

The importance of this distinction is that if certain cells
rejuvenate when they divide, we could look for a sudden cascade
of DNA and protein repair enzymes, and other restorative
molecules within the cell when it prepares to divide. If not,
then we have to examine the differences between immortal cells,
and cells that don't eliminate aging when they divide.

Dr. Michael West (CEO of Applied Cell
Technology) discusses it in the interview "On Living Forever"
that he gave in the June, 2000, issue of Ubiquity
Magazine.2
So the information is out there. The only question is: why
don't you hear more about it? To me, it was a revelation on a par
with Hahn and Strassman's splitting of the uranium atom in
1939...a discovery so momentous that governments of that era
raced to capitalize upon it. The $$$ involved in total
rejuvenation would be mind-boggling, together with momentous
implications for society. My guess is that even if this can occur
only in fertilized ova, there are mechanisms -- e. g., DNA repair
mechanisms --that can probably be pressed into service to
rejuvenate adult cells. Of course, neurons and myocytes are
post-mitotic, and don't divide, so they might be restored to a
virgin state, but I wouldn't expect missing cells to be replaced.
That would require some other maneuver... viz., stem cell
infusions.

Some Mechanisms of Aging

Telomeres -- The DNA Replication Counter

One of the mechanisms of aging is the "replication counter"
embodied in the telomeres. The telomeres are caps on the ends of
chromosomes that keep them from fraying. For differentiated,
dividing cells, the telomeres shorten each time the cell divides.
Eventually, the telomeres become very short, and irregularities
in cell division and function begin to occur. Finally, the
telomeres vanish, and further cell division is impossible. The
maximum number of divisions allowed varies from species to
species. In humans, about 80 to 90 divisions are possible in
vitro.

The telomeres can be restored with a ribonucleoprotein called
telomerase.Telomerase is missing in most human somatic cells,
although it's present in human germ cells and in cancer cells.

However, telomeres don't normally get short enough in humans to
halt cell division. Also, the post-mitotic (non-dividing) cells
found in central nervous tissue and muscle tissue don't divide,
anyway, so any aging that occurs in them must have nothing to do
with the shortening of the telomeres (although a loss of
effectiveness of
supporting tissue could hamper them).

Glycation - Damage to Proteins

Glycation is sometimes called the "browning" reaction because
it's like the browning of meat, or the yellowing of paper.
Cross-linking of the proteins contributes strongly to
cardiovascular disease, kidney disease, arthritis, stiffening of
the skin, cataracts, complications of diabetes, and Alzheimer's
Disease. Aspirin and carnosine seem to slow the development of
Advanced Glycation End products (AGE's). Crosslink breakers
similar to vitamin B1 are under development. The furthest along
is 3-phenacyl-4, 5-dimethl-thiazolium chloride, developed by
Alteon Pharmaceuticals and showing promise in Phase 2 clinical
trials.

Lipofucsin (Sludge) Build-Up in the Lysosomes (Recycling Plants)
of Cells

Lipofucsin or ceroid is a highly cross-linked product found in
the lysosomes or recycling plants of non-dividing cells. This
indigestible sludge builds up until it can interfere with the
recycling of waste products in the cell, and may even cause
leakage of the highly reactive breakdown enzymes from the
lysosomes into the surrounding cytoplasm, with harmful results.

Mutated Mitochondrial DNA

The mitochondria are the powerhouses of cells, converting sugars
into a form that can be used to fuel cells. The mitochondria and
the lysosomes are "hot spots" within the cell containing very
corrosive molecules. If they don't function properly, they can
cause a lot of mischief.

What's Available for You Right Now for the Possible Retardation
of Aging?

Total rejuvenation is an extreme case of the gradual extension of
the life span and of the "youth span" of the average person that
has occurred over the past few hundred years. Various forms of
additional extension of the average life span are possible,
ranging from better health habits, to caloric restriction, to,
possibly, some kinds of "prolongevity" interventions.

Are Our Lifespans Written in Our Genes?

I don't have a solid answer to that. A search on Google for
"identical twins"/lifespan yielded conflicting results. A couple
of reports said that 35% of lifespan variability is genetically
determined, and 65% is environmentally modulated. On average,
twins dates of death are 7 years apart. On the other hand, 60% of
all centenarians had at least one close relative who had also
been a centenarian. In my own family, there was one uncle who
smoked like a furnace and drank like a fish until he was 76, Then
his doctor told him he could either quit or die. He chose to
quit, and died at 90. He had a younger brother who died in his
early 70's of a stroke. Aunt Florence was a health food
enthusiast and died at 94. Uncle Glen was still cracking jokes
and driving his truck until a few days before he died (of a
stroke) at 95. He scoffed at health foods, and loved meat,
potatoes, and gravy. There was Aunt Ava, who was very overweight
and loved pop tarts. It eventually killed her, at 90. Aunt Addie
was on the pudgy side and died at 100. But Aunt Gertrude died of
breast cancer at 76. Of course, there's no way of knowing whether
Uncle Glen and Aunt Ava could have lived a few years longer had
they taken better care of their health.

I think there's something to the genetic model, but I think that
environment also plays a role. Alcoholics and high rollers often
die in their forties. Lung cancer often hits in the fifties and
sixties. And when it comes to these supplements, we're on virgin
ground. In animal studies, feeding animals antioxidants elevates
the average age of death, but not the maximum life span. However,
raising the average life span (if indeed they can do this) would
be quite fine. Here. though, some of these supplements might
possibly modulate the rate of aging, since they contain more than
merely antioxidants.

Diabetes was a certain death sentence in 1900. Today, many
diabetics can control their diabetes with diet alone. In 1900, a
family history of hypertension or heart disease was an almost
certain sentence of early death. Today, there's a great deal we
can do to extend the lifespans of people with such
predispositions, even to the point of achieving normal lifespans.

What I believe is that better diet and medical interventions may
reduce your risks of cancer, cardiovascular disease, Alzheimer's
Disease, and Parkinson's Disease. And right now, the name of the
game is to hold on while improvements in aging intervention
appear.

The Guidelines Are Shifting From Low-Fat to Low-Calorie

Twenty years ago, the dietary emphasis for healthy living was
centered around low-fat diets. Low-fat diets are still "in", but
the principal cause of aging is now considered to lie in the
calories that we consume. Free radicals, primarily involving
oxygen, and primarily produced by energy generation in the
mitochondria, are considered to be to the drivers of aging. The
ingestion of various kinds of antioxidants is a crucial component
of early 21st-century aging-mitigation programs.

Let's see what's out there for you now, and what's in the
pipeline for the near future. First of all, you can extend your
youth span by avoiding activities that are obviously harmful to
you. For example, sunlight is devastating to your skin. A tan
(not just a sunburn) is a mark of DNA damage to your skin.
Second, you can eat foods that may protect you from cancer.
Generally, these are foods containing antioxidants, such as
brightly colored fruits and vegetables. New foods are being added
as time goes by. Two servings of fish a week are suggested, with
one of them being one of the fatty thalassic fish containing the
omega-3 fatty acids, such as salmon, tuna, mackerel, or whitefish
(but not cod). (A British health watch organization has just
warned against eating more than one serving of fatty fish a week
because of the PCB's, dioxin, and mercury in them.)

Among the older recommended foods are broccoli, cabbage, spinach,
and carrots. Apples, oranges, purple grapes, and recently,
strawberries and blueberries have been added to this list. Green
tea is being recommended for its beneficial properties. (You can
buy the essences of many of these fruits and herbs at Walmart.)

Third, you can take nutritional supplements that
may also, hopefully, afford cancer protection as well as
resistance to aging. Here, there are as many expert opinions as
there are experts. Three sets of recommendations are presented in
the Table on page 12. In the first column below are Maximum Life
Foundation's daily dosage recommendations of supplements, based
upon suggestions from Dr. Lester Packer. Dr. Karlis Ullis, and
the Life Extension Foundation.3
In the second column below are the daily
supplements that John Furber is
taking.4
The third column contains the ingredients in the
Life Extension Foundation's Life Extension
Mix.5

As you can see, there's no universal agreement regarding what
supplements one should take. One factor to consider is the cost
of these "nutritionals". Costs would eat you alive if you tried
to buy all of these supplements individually. For this reason,
the "Life Extension Mix" from the Life Extension Foundation
sounds promising to me. It's advertised as costing $1.36 a day
(plus the annual cost of membership in the Life Extension
Foundation). That might sound like a lot, but when you consider
the cost of buying even a fraction of this at Walmart (let alone
a health boutique), it begins to look like a pretty good deal.
I'm not prepared to recommend anything at this time because I
don't yet know that much about these choices.

In any case, if you're going to buy nutritional supplements, and
most people do these days, then the three of these supplement
lists are probably a better choice than what's available at
Walmart. You could probably find all this at your local health
food store, but it would cost you an arm and a leg.

Dimericine

One product that is wending its way to market is
Dimericine ("New cream may repair sun damage to
skin".6
Dimericine is a cream containing a DNA repair
agent harvested from pelagic bacteria and algae, and delivered
via a viral transfection agent. Dimericine is in Phase IV FDA
testing, and has been shown to reduce the incidence of skin
cancers by about one-third, and of actinic keratoses by about
two-thirds. The company that developed it, Applied Genetics, Inc.
-- Dermatics, has licensed cosmetic rights to a company called
Elan Pharmaceuticals with the hope of eventually including
Dimericine in suntan lotions. (It may prove to be too expensive
for that purpose.) In the meantime, two companies are selling a
"DNA repair cream" (both are selling the same cream and are
making the same claim) that is ostensibly Dimericine, although
they don't claim that on the bottle. I'm trying it on my left
hand, and on the left side of my face. The results are too early
to call just yet. The cream is very expensive, running $45 a
bottle plus $10 S&H from Synergy, or £21.99 + £3.50
S&H from Apple Healthcare in the UK.

Other "Dermaceuticals"

A companion product was discussed on a recent ABC documentary. It
would appear that there are now several treatments that will
actually reverse aging in skin. Tommie Jean happened to be tuned
in to the original TV program when it was shown on ABC night
before last. They showed before and after pictures taken in a
research study of a stem-cell cream, and pointed out the
(visible) changes in women's jaw lines and sagging jowls that
were firmed up by their experimental cream. There were also two
other approaches described in the article and presented visually
in the TV special. I haven't tried them yet, but I may.

As I understand it, these biological agents partially and
"permanently" (for many years) reverse aging in skin. Of course,
the next question that crosses your mind is: What would happen if
you were to take it internally? I presume that's been attempted
with animal models. (I certainly wouldn't want to be the first
one to try it.)

Acetyl-l-Carnitine and Alpha-Lipoic Acid

Dr. Bruce Ames, et al, recently reported in three articles in the
Proceedings of the National Academy of Sciences that the
simultaneous administration of two naturally occurring food
supplements, acetyl-l-carnitine and alpha-lipoic acid, had

extended the maximum life spans of laboratory rats by about 50%.
Dr. Ames and his colleagues were repeating similar studies
performed by other researchers, who obtained similar results. Dr.
Ames is known for his Ames Test of Mutagenicity.) Carnitine and
lipoic acid are members of the B-vitamin family found in red
meat.

Recommended Nutritional Supplements

Ingredient

Max Life

John Furber

Life
Ext. Mix

Beta Carotene

5-20 mg.

--

10,000 IU

Vitamin B1

500 mg.

200 mg.

125 mg.

Vitamin B2

100-200 mg.

200 mg.

50 mg.

Vitamin B3

100-200 mg.

300 mg.

187 mg.

Niacinamide

--

140 mg.

(incl. above)

Vitamin B5

500-1,500 mg.

1,000 mg.

600 mg.

Vitamin B6

250 mg.

200 mg.

100 mg.

Vitamin B12

300-500 mg.

200 mg.

600 mcg.

Folic Acid

800 mg.

1,600 mcg. (w/B12)

800 mcg.

Vitamin C

500-1,500 mg.

3,000 mg.

2,605 mg.

Ascorbyl Pal.

--

600 mg.

250 mg.

Citrus Biofl.

--

--

1,300 mg.

Vitamin D3

--

400 IU

400 IU

Vitamin E (mixed)

500 mg.

1,000 IU

400 IU

Calcium

--

1,345 mg.

227 mg.

Chromium

200-400 mcg.

200 mcg.

200 mcg.

Magnesium

--

592 mg.

325 mg.

Selenium

200-400 mcg.

150 mcg.

200 mcg.

Zinc

--

60 mg.

35 mg.

Copper

--

--

1 mg.

Manganese

--

--

5 mg.

Molybdenum

--

--

125 mcg.

Coenzyme Q-10

30-90 mg.

50-100 mg.

--

Lutein

1,000 mg.

--

15 mg.

Lycopene

--

--

3 mg.

Carnosine

--

100 mg.

--

N-Acetyl-i-Cy.

--

1,000 mg.

600 mg.

L-Lysine HCl

--

900 mg.

500 mg.

Methionine

--

120 mg.

--

L-Taurine

--

--

500 mg.

L-Phenylalan.

--

325 mg.

--

Phosphatidych.

--

--

150 mg.

Tommie and I have been taking acetyl-l-carnitine and alpha-lipoic
acid for about six months. Does it make a difference? Of course,
it's very hard to say. I don't know how we would feel without it.
(We've upped our dosage of acetyl-l-carnitine to 500 mg. a day
and of alpha-lipoic acid to 300 mg. a day, since this seems to be
the "going dosage".

2 comments:

I hate to admit it but sometimes I just get a little mystified by people's responses to input, or rather the lack of it. This is an important and interesting subject. The essay has been up a year, surely seen by many thousands. Not a single comment.

As it happens, prompted my own empirical research in dealing with diverse problems such as a stroke two years ago, a periodontal emergency a year ago, a serious cataract and several lesser health issues, I am already taking most of the things in your list, perhaps not in exactly in the amounts listed, but in the same ballpark. On top of that, I am doing some things which have not been included in your essay, some of which I have not written about yet because I am still in the experimentation phase with them.

The point is, what you have presented here is quite useful. It is distressing that no one, in this amount of time has told you so.

My blog currently has some sixty or so essays on a wide variety of topics. I get an average of about one written comment a month posted.I have been taking that rather personally. Before I lost my counter in a computer crash, I had had several thousand hits, having no expertise to increase traffic. I am essentially not a computer whiz.

But I should not have been the first to tell you that you have made a useful presenation.

All you silent lurkers out there, what IS your problem? Don't you think it would be a good idea to encourage this sort of work?

I have actually gotten more responses to my work from local people who I know in person, telling me what they think than I have gotten as blog comments, perhaps by a factor of four.

Life is but a vapor that appears for a little time and then vanishes away. Life is as the flower of grass, the grass withereth, and the flower therof, fadeth away. It is appointed unto man once to die, and after this is the judgement. Live the life God gives you, to his glory, and you will be glad to go to him. Precious in the eyes of the Lord is the death of one of his saints.

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